Bone material hydration devices and methods

ABSTRACT

A device for hydrating particulate bone material is provided. The device comprises a tubular member having an interior surface and an exterior surface. The interior surface is configured to receive the particulate bone material and a hydration fluid. The exterior surface has a plurality of pores configured to allow the hydration fluid to flow into the interior surface of the tubular member and hydrate the particulate bone material. The plurality of pores are smaller in size than the particulate bone material. Methods of dispensing particulate the bone material are also provided.

BACKGROUND

The use of bone material including natural bone and bone substitutematerials for filling a bone repair site in orthopedic medicine isknown. While bone wounds can regenerate without the formation of scartissue, fractures and other orthopedic injuries take a long time toheal, during which time the bone is unable to support physiologicloading unaided. Metal pins, screws, rods, plates and meshes arefrequently required to replace the mechanical functions of injured bone.However, metal is significantly more stiff than bone. Use of metalimplants may result in decreased bone density around the implant sitedue to stress shielding. Physiologic stresses and corrosion may causemetal implants to fracture. Unlike bone, which can heal small damagecracks through remodeling to prevent more extensive damage and failure,damaged metal implants can only be replaced or removed. The naturalcellular healing and remodeling mechanisms of the body coordinateremoval of bone and bone grafts by osteoclast cells and formation ofbone by osteoblast cells.

Conventionally, bone tissue regeneration is achieved by filling a bonerepair site with a bone graft. Over time, the bone graft is incorporatedby the host and new bone remodels the bone graft. A bone graft can bemade from various bone particulate having various particle sizes, suchas, for example, fine bone particulate. However, handling of fineparticulate bone material can be difficult due to its consistency. Inorder to insert the bone material, it is common to use a deliveryinstrument.

Currently, there are various delivery instruments used for bone materialdelivery, however, not many instruments can handle bone material whenthe bone material is fine particulate bone material. Further, the bonematerial can be difficult to package and re-hydrate. Components of thebone material can also be wasted during the packaging and re-hydratingprocess and allow contamination of the bone material during packing andhydration of the bone material as a result of several manipulatingsteps.

Therefore, it would be beneficial to provide devices for effectivelyhydrating particulate bone material which can be used for administeringthe particulate bone material to a surgical site. Methods of hydratingand kits to hydrate bone material would also be beneficial.

SUMMARY

Devices and methods are provided for hydrating particulate bonematerial. The hydrated particulate bone material can be delivered to asurgical site via a delivery instrument. The device packs, hydrates anddelivers particulate bone material. In one embodiment, a device forhydrating particulate bone material is provided. The device comprises atubular member having an interior surface and an exterior surface. Theinterior surface is configured to receive the particulate bone materialand a hydration fluid. The exterior surface has a plurality of poresconfigured to allow the hydration fluid to flow into the interiorsurface of the tubular member and hydrate the particulate bone material.The plurality of pores are smaller in size than the particulate bonematerial.

In some embodiments, a device for hydrating particulate bone material isprovided. The device comprises a tubular member having an interiorsurface configured to receive the particulate bone material and ahydration fluid. The tubular member includes a proximal end openingconfigured to receive a syringe, and a distal end opening configured toreceive a cap. The cap has a plurality of pores configured to allow thehydration fluid to flow into the interior surface of the tubular memberand hydrate the particulate bone material. The plurality of pores on thecap are smaller in size than the particulate bone material.

In some embodiments, a method of dispensing particulate bone material ata surgical is provided. The method comprises loading a device forhydrating the particulate bone material, the device comprising a tubularmember having an interior surface and an exterior surface, the interiorsurface configured to receive the particulate bone material and ahydration fluid, the exterior surface having a plurality of poresconfigured to allow the hydration fluid to flow into the interiorsurface of the tubular member and hydrate the particulate bone material,the plurality of pores being smaller in size than the particulate bonematerial; immersing the device in a fluid filled bath; and engaging thedevice with a cannula and a plunger to dispense the particulate bonematerial to the surgical site.

While multiple embodiments are disclosed, still other embodiments of thepresent application will become apparent to those skilled in the artfrom the following detailed description, which is to be read inconnection with the accompanying drawings. As will be apparent, thepresent disclosure is capable of modifications in various obviousaspects, all without departing from the spirit and scope of the presentdisclosure. Accordingly, the detailed description is to be regarded asillustrative in nature and not restrictive.

BRIEF DESCRIPTION OF THE FIGURES

The present disclosure will become more readily apparent from thespecific description accompanied by the following drawings, in which:

FIG. 1 is a front view of one embodiment of a device for hydrating aparticulate bone material. The device comprises a tubular member havingan interior surface configured to receive the particulate bone materialand a hydration fluid. The tubular member also includes an exteriorsurface having a plurality of pores configured to allow the hydrationfluid to flow into the interior surface of the tubular member andhydrate the particulate bone material. The plurality of pores aresmaller in size than the particulate bone material. The tubular membercomprises a proximal end opening configured to receive the bone materialand a removable distal end configured to form a distal end opening todispense the particulate bone material. In this embodiment, the deviceis shown engaging with a funnel and being loaded with the bone material.

FIG. 2 is front view of the device of FIG. 1. In this embodiment, thedevice includes a rigid collar to facilitate loading and attachment tobone delivery instruments.

FIG. 3 is a perspective view of the device of FIG. 1 immersed in a fluidfilled bath to hydrate the bone material.

FIG. 4 is a front view of the device of FIG. 1 after hydration in thefluid filled bath of FIG. 3. In this embodiment, the device is disposedwith a delivery instrument. The collar of the device matingly engageswith an end of the delivery instrument.

FIG. 5 is a front view of the bone material delivery device of FIG. 4disposed with the delivery instrument. In this embodiment, a plunger isinserted at the proximal end of the device and into the deliveryinstrument to dispense the bone material to a surgical site.

FIG. 6 is a side view of one embodiment of a device for hydrating aparticulate bone material. In this embodiment, the tubular member of thedevice comprises a one-way valve and a port configured to receive asyringe. Further, the interior surface of the tubular member at aproximal end comprises threading to engage with a threaded outer surfaceof a plunger.

FIG. 7 is a side view of the plunger that engages with the device ofFIG. 6.

FIG. 8 is a front view of the syringe that engages with the port of thedevice of FIG. 6.

FIG. 9 is a side view of the device of FIG. 6. FIG. 9 shows the plungerof FIG. 7 engaging with the proximal end of the device and the syringeof FIG. 8 engaging with the port of the device. The plunger of thesyringe is moved in an upward direction to draw air and/or fluid out ofthe tubular member, thereby creating negative pressure in the tubularmember. The plunger is then moved in a downward direction such that thehydrated particulate bone material is dispensed from the tubular member.

FIG. 10 is a front view of one embodiment of a device for hydrating abone material. The device comprises a tubular member having an interiorsurface configured to receive the particulate bone material and ahydration fluid. The tubular member includes a proximal end openingconfigured to receive a syringe, and a distal end opening configured toreceive a cap. The cap including a plurality of pores configured toallow the hydration fluid to flow into the interior surface of thetubular member and hydrate the particulate bone material. The pluralityof pores are smaller in size than the particulate bone material. In thisembodiment, the proximal end opening engages with a cap comprising aluer fitting that engages with the syringe. The cap including aplurality of pores will draw fluid from a fluid filled bath into thepores of the cap and into the device when the syringe is moved in anupward direction to hydrate the bone material.

FIG. 11 is a front view of the bone material delivery device of FIG. 10.In this embodiment, the syringe and caps are removed from both ends ofthe device.

FIG. 12 is a front view of the bone material delivery device of FIG. 10where the device is ready to be loaded into a delivery instrument fordelivery of the bone material to a surgical site.

It is to be understood that the figures are not drawn to scale. Further,the relation between objects in a figure may not be to scale, and may infact have a reverse relationship as to size. The figures are intended tobring understanding and clarity to the structure of each object shown,and thus, some features may be exaggerated in order to illustrate aspecific feature of a structure.

DETAILED DESCRIPTION Definitions

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing quantities of ingredients,percentages or proportions of materials, reaction conditions, and othernumerical values used in the specification and claims, are to beunderstood as being modified in all instances by the term “about.”Similarly, when values are expressed as approximations, by use of theantecedent “about,” it will be understood that the particular valueforms another embodiment that is +/−10% of the recited value.Accordingly, unless indicated to the contrary, the numerical parametersset forth in the following specification and attached claims areapproximations that may vary depending upon the desired propertiessought to be obtained by the present disclosure. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical parameter shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques. Also, as used inthe specification and including the appended claims, the singular forms“a,” “an,” and “the” include the plural, and reference to a particularnumerical value includes at least that particular value, unless thecontext clearly dictates otherwise. Ranges may be expressed herein asfrom “about” or “approximately” one particular value and/or to “about”or “approximately” another particular value. When such a range isexpressed, another embodiment includes from the one particular valueand/or to the other particular value.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of this application are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Moreover, all ranges disclosed hereinare to be understood to encompass any and all subranges subsumedtherein. For example, a range of “1 to 10” includes any and allsubranges between (and including) the minimum value of 1 and the maximumvalue of 10, that is, any and all subranges having a minimum value ofequal to or greater than 1 and a maximum value of equal to or less than10, for example, 5.5 to 10.

The bone material can have a bioactive agent mixed with it. Bioactiveagent or bioactive compound is used herein to refer to a compound orentity that alters, inhibits, activates, or otherwise affects biologicalor chemical events. For example, bioactive agents may include, but arenot limited to, osteogenic or chondrogenic proteins or peptides,anti-AIDS substances, anti-cancer substances, antibiotics,immunosuppressants, anti-viral substances, enzyme inhibitors, hormones,neurotoxins, opioids, hypnotics, anti-histamines, lubricants,tranquilizers, anti-convulsants, muscle relaxants and anti-Parkinsonsubstances, anti-spasmodics and muscle contractants including channelblockers, miotics and anti-cholinergics, anti-glaucoma compounds,anti-parasite and/or anti-protozoal compounds, modulators ofcell-extracellular matrix interactions including cell growth inhibitorsand antiadhesion molecules, vasodilating agents, inhibitors of DNA, RNAor protein synthesis, anti-hypertensives, analgesics, anti-pyretics,steroidal and non-steroidal anti-inflammatory agents, anti-angiogenicfactors, angiogenic factors, anti-secretory factors, anticoagulantsand/or antithrombotic agents, local anesthetics, ophthalmics,prostaglandins, anti-depressants, anti-psychotic substances,anti-emetics, and imaging agents. In certain embodiments, the bioactiveagent is a drug. Bioactive agents further include RNAs, such as siRNA,and osteoclast stimulating factors. In some embodiments, the bioactiveagent may be a factor that stops, removes, or reduces the activity ofbone growth inhibitors. In some embodiments, the bioactive agent is agrowth factor, cytokine, extracellular matrix molecule or a fragment orderivative thereof, for example, a cell attachment sequence such as RGD.A more complete listing of bioactive agents and specific drugs suitablefor use in the present application may be found in PharmaceuticalSubstances: Syntheses, Patents, Applications by Axel Kleemann and JurgenEngel, Thieme Medical Publishing, 1999; Merck Index: An Encyclopedia ofChemicals, Drugs, and Biologicals, edited by Susan Budavari et al., CRCPress, 1996; and United States Pharmacopeia-25/National Formulary-20,published by the United States Pharmacopeia Convention, Inc., RockvilleMd., 2001, each of which is incorporated herein by reference. In someembodiments, bioactive agents include nutrients, oxygen sources, andhypoxic inducers such as carbon monoxide or iron chelators.

Biocompatible, as used herein, is intended to describe materials that,upon administration in vivo, do not induce undesirable long-termeffects.

Bone material includes material derived from natural bone and/orsynthetic bone. Synthetic bone includes, but is not limited tobiomaterials that contain hydroxyapatite, calcium phosphate, silicatematerials, cements, polymers, collagen sheets, fibers, granules,alginate, starch, and/or PLGA. In some embodiments, the bone materialcan be ceramic/synthetic bone void fillers and can contain animalderived collagen elements. In some embodiments, various MasterGraft®products produced by Medtronic Sofamor Danek, Inc., Memphis, Tenn. canbe used as the bone material. The bone material can be in particulateform such as, for example, chips, fibers, powder or a combinationthereof. Bone, as used herein, refers to bone that is cortical,cancellous or cortico-cancellous of autogenous, allogenic, xenogenic, ortransgenic origin.

Demineralized, as used herein, refers to any material generated byremoving mineral material from tissue, for example, bone tissue. Incertain embodiments, demineralized bone material may be added to thebone void filler. The demineralized bone material described hereininclude preparations containing less than 5%, 4%, 3%, 2% or 1% calciumby weight. Partially demineralized bone (for example, preparations withgreater than 5% calcium by weight but containing less than 100% of theoriginal starting amount of calcium) is also considered within the scopeof the disclosure. In some embodiments, partially demineralized bonecontains preparations with greater than 5%, 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%,97%, 98% or 99% of the original starting amount of calcium. In someembodiments, demineralized bone has less than 95% of its originalmineral content. In some embodiments, demineralized bone has less than95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%,25%, 20%, 15%, 10%, or 5% of its original mineral content. Demineralizedis intended to encompass such expressions as “substantiallydemineralized,” “partially demineralized,” “superficiallydemineralized,” and “fully demineralized.” In some embodiments, part orall of the surface of the bone can be demineralized. For example, partor all of the surface of the bone material can be demineralized to adepth of from about 100 to about 5000 microns, or about 150 microns toabout 1000 microns. In some embodiments, part or all of the surface ofthe bone material can be demineralized to a depth of from about 100,150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800,850, 900, 950, 1000, 1050, 1100, 1150, 1200, 1250, 1300, 1350, 1400,1450, 1500, 1550, 1600, 1650, 1700, 1750, 1800, 1850, 1900, 1950, 2000,2050, 2100, 2150, 2200, 2250, 2300, 2350, 2400, 2450, 2500, 2550, 2600,2650, 2700, 2750, 2800, 2850, 2900, 2950, 3000, 3050, 3100, 3150, 3200,3250, 3300, 3350, 3400, 3450, 3500, 3550, 3600, 3650, 3700, 3750, 3800,3850, 3900, 3950, 4000, 4050, 4100, 4150, 4200, 4250, 4300, 4350, 4400,4450, 4500, 4550, 4600, 4650, 4700, 4750, 4800, 4850, 4900, 4950 toabout 5000 microns. If desired, the bone material can comprisedemineralized material.

Partially demineralized bone is intended to refer to preparations withgreater than 5% calcium by weight but containing less than 100% of theoriginal starting amount of calcium. In some embodiments, partiallydemineralized bone comprises 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98 and/or 99% of the originalstarting amount of calcium.

In some embodiments, the demineralized bone may be surface demineralizedfrom about 1-99%. In some embodiments, the demineralized bone is 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76,77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 96, 97, 98 and/or 99% surface demineralized. In various embodiments,the demineralized bone may be surface demineralized from about 15-25%.In some embodiments, the demineralized bone is 15, 16, 17, 18, 19, 20,21, 22, 23, 24 and/or 25% surface demineralized.

Demineralized bone matrix (DBM), as used herein, refers to any materialgenerated by removing mineral material from bone tissue. In someembodiments, the DBM compositions as used herein include preparationscontaining less than 5% calcium and, in some embodiments, less than 1%calcium by weight. In some embodiments, the DBM compositions includepreparations that contain less than 5, 4, 3, 2 and/or 1% calcium byweight. In other embodiments, the DBM compositions comprise partiallydemineralized bone (for example, preparations with greater than 5%calcium by weight but containing less than 100% of the original startingamount of calcium).

Osteoconductive, as used herein, refers to the ability of a substance toserve as a template or substance along which bone may grow.

Osteogenic, as used herein, refers to materials containing living cellscapable of differentiation into bone tissue.

Osteoinductive, as used herein, refers to the quality of being able torecruit cells from the host that have the potential to stimulate newbone formation. Any material that can induce the formation of ectopicbone in the soft tissue of an animal is considered osteoinductive. Forexample, most osteoinductive materials induce bone formation in athymicrats when assayed according to the method of Edwards et al.,“Osteoinduction of Human Demineralized Bone: Characterization in a RatModel,” Clinical Orthopaedics & Rel. Res., 357:219-228, December 1998,incorporated herein by reference.

Superficially demineralized, as used herein, refers to bone-derivedelements possessing at least about 90 weight percent of their originalinorganic mineral content. In some embodiments, superficiallydemineralized contains at least about 90, 91, 92, 93, 94, 95, 96, 97, 98and/or 99 weight percent of their original inorganic material. Theexpression “fully demineralized” as used herein refers to bonecontaining less than 8% of its original mineral context. In someembodiments, fully demineralized contains about less than 8, 7, 6, 5, 4,3, 2 and/or 1% of its original mineral content.

The expression “average length to average thickness ratio” as applied tothe DBM fibers of the present application means the ratio of the longestaverage dimension of the fiber (average length) to its shortest averagedimension (average thickness). This is also referred to as the “aspectratio” of the fiber.

Fibrous, as used herein, refers to bone elements whose average length toaverage thickness ratio or aspect ratio of the fiber is from about 50:1to about 1000:1. In some embodiments, average length to averagethickness ratio or aspect ratio of the fiber is from about 50:1, 75:1,100:1, 125:1, 150:1, 175:1, 200:1, 225:1, 250:1, 275:1, 300:1, 325:1,350:1, 375:1, 400:1, 425:1, 450:1, 475:1, 500:1, 525:1, 550:1, 575:1,600:1, 625:1, 650:1, 675:1, 700:1, 725:1, 750:1, 775:1, 800:1, 825:1,850:1, 875:1, 900:1, 925:1, 950:1, 975:1 and/or 1000:1. In overallappearance, the fibrous bone elements can be described as bone fibers,threads, narrow strips, or thin sheets. Often, where thin sheets areproduced, their edges tend to curl up toward each other. The fibrousbone elements can be substantially linear in appearance or they can becoiled to resemble springs. In some embodiments, the bone fibers are ofirregular shapes including, for example, linear, serpentine or curvedshapes. The bone fibers are demineralized, however some of the originalmineral content may be retained when desirable for a particularembodiment. In various embodiments, the bone fibers are mineralized. Insome embodiments, the fibers are a combination of demineralized andmineralized.

Non-fibrous, as used herein, refers to elements that have an averagewidth substantially larger than the average thickness of the fibrousbone element or aspect ratio of less than from about 50:1 to about1000:1. The non-fibrous bone elements are shaped in a substantiallyregular manner or specific configuration, for example, triangular prism,sphere, cube, cylinder and other regular shapes. By contrast, particlessuch as chips, shards, or powders possess irregular or randomgeometries. It should be understood that some variation in dimensionwill occur in the production of the elements of this application andelements demonstrating such variability in dimension are within thescope of this application and are intended to be understood herein asbeing within the boundaries established by the expressions “mostlyirregular” and “mostly regular.”

Percutaneous, as used herein, refers to a surgical method where entry tothe spine is by puncture or minor incision, of instrumentation throughthe skin or mucous membrane and/or any other body layers necessary toreach the site of the procedure.

The devices, bone materials, kits and methods may be employed to treatspinal disorders such as, for example, degenerative disc disease, discherniation, osteoporosis, spondylolisthesis, stenosis, scoliosis andother curvature abnormalities, kyphosis, tumor and fractures. Thedevices, bone materials, kits and methods may be employed with otherosteal and bone related applications, including those associated withdiagnostics and therapeutics. They may also be alternatively employed ina surgical treatment with a patient in a prone or supine position,and/or employ various surgical approaches to the spine, includinganterior, posterior, posterior mid-line, direct lateral,postero-lateral, and/or antero-lateral approaches, and in other bodyregions. The devices, bone materials, kits and methods may also bealternatively employed with procedures for treating the lumbar,cervical, thoracic, sacral and pelvic regions of a spinal column. Theymay also be used on animals, bone models and other non-livingsubstrates, such as, for example, in training, testing anddemonstration.

In various embodiments, the bone material comprisespoly(lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide(PGA), D-lactide, D,L-lactide, L-lactide, D,L-lactide-co-ε-caprolactone,D,L-lactide-co-glycolide-co-ε-caprolactone, L-lactide-co-ε-caprolactoneor a combination thereof.

In some embodiments, the devices, bone materials, kits and methods areused in minimally invasive surgeries and the bone material ispercutaneously delivered to a surgical site or the surgical site is theposterior spine.

Devices

Referring to FIGS. 1 to 5, a device 20 is provided for hydratingparticulate bone material 22 (e.g., bone graft). The device isconfigured to hydrate the particulate bone material prior to loading ofthe particulate bone material into a delivery instrument. The hydratedparticulate bone material is fully contained in the device and is thenloaded into a delivery instrument for administration to a surgical site.

The device includes a tubular member 24 having an interior surface 26and an exterior surface 28, as shown in FIG. 2. The interior surfacedefines a channel 29 and is configured to receive the particulate bonematerial and a hydration fluid 30. The exterior surface of the tubularmember includes a plurality of pores 32 configured to allow thehydration fluid to flow into the interior surface of the tubular memberand hydrate the particulate bone material, as described herein. Theplurality of pores are smaller in size than the particulate bonematerial. In some embodiments, the plurality of pores have a pore sizefrom about 10 to about 100 microns, from about 20 to about 80 microns,or from about 40 to about 60 microns. In some embodiments, the pluralityof pores can have a pore size from about 10, 12, 14, 16, 18, 20, 22, 24,26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60,62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96,98 to about 100 microns. In some embodiments, the plurality of pores canbe the same or various sizes throughout the tubular member, theplurality of pores can be larger when disposed at a distal end, can beuniform throughout or can be larger in distinct zones on the exteriorsurface of the tubular member.

In some embodiments, when the bone material contained in the tubularmember is fibrous instead of particulate, the plurality of pores can bemade larger than the diameter of the fibers but smaller than the overalllength of the fibers, thus restricting the fibers from exiting throughthe plurality of pores. In some embodiments, when the bone material isfibrous, the longer the fibers, the more entangled the fibers willbecome, therefore further preventing the fibers from exiting through theplurality of pores which enables the plurality of pores to be evenlarger than if the bone material was made from particulate bone.

In some embodiments, when a specific level of hydration is required forthe bone material, the plurality of pores can be used to evacuatesurplus hydration.

In some embodiments, the plurality of pores can be a circular hole orholes where a plug or plugs (not shown) of the tubular member has beenremoved. In some embodiments, the plurality of pores can be a cut orcuts in a side of the tubular member to break tubular member continuity.The cut or cuts can be a single point break, such as a pin prick, ahorizontal, vertical or angled slit formed by slicing the tubularmember, or semi-circular patterns cut into the tubular member to formflaps. The flaps can be biased into a particular direction to facilitatehydration or flow of bone material when the bone material is dispensedfrom the tubular member.

In some embodiments, the plurality of pores can be one-way pores suchthat fluid is permitted to enter the tubular member, but then, as aplunger is used to dispense the bone material, the plurality of porescan close to prevent the bone material or fluid from exiting through theplurality of pores. This would also allow pressurization of the bonematerial in the tubular member, and allow more intimate hydration of thebone material.

The tubular member comprises a proximal end 34 defining a proximal endopening 36, a distal end 38 defining a distal end opening 40 and alongitudinal axis AA disposed therebetween. The proximal end opening isconfigured to receive the particulate bone material and the distal endopening is configured to dispense the particulate bone material.

The tubular member can have a length L1, a width W1 at the proximal endand a width W2 at the distal end. The length L1 can be from about 1 inchto about 20 inches, from about 1 to about 15 inches, from about 1 toabout 10 inches, from about 1 to about 5 inches, from about 5 to about20 inches, from about 5 to about 15 inches, from about 5 to about 10inches, from about 10 to about 20 inches, from about 10 to about 15inches, or from about 15 to about 20 inches. In some embodiments, thelength L1 can be from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19 to about 20 inches.

In some embodiments, widths W1 and W2 can be from about 0.5 to about 5inches, from about 1 inch to about 5 inches, from about 1 to about 4inches, from about 1 to about 3, from about 1 to about 2 inches, fromabout 2 to about 5 inches, from about 2 to about 4 inches, from about 2to about 3 inches, from about 3 to about 5 inches or from about 4 toabout 5 inches. In some embodiments, widths W1 and W2 can be from about0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9,2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4,3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9to about 5 inches. In some embodiments, widths W1 and W2 can be the sameor different sizes.

The tubular member comprises a removable distal end 42 configured toform the distal end opening to dispense the particulate bone material.In some embodiments, the removable distal end can be a sealed end. Thesealed end can be sealed via heat and/or adhesive. In some embodiments,the sealed end can be sealed via adhesives including, but not limited tocyanoacrylates (such as histoacryl, B Braun, which is n-butyl-2cyanoacrylate; or Dermabond, which is 2-octylcyanoacrylate), epoxy-basedcompounds, dental resin sealants, dental resin cements, glass ionomercements, polymethyl methacrylate, gelatin-resorcinol-formaldehyde glues,collagen-based glues, inorganic bonding agents such as zinc phosphate,magnesium phosphate or other phosphate-based cements, zinc carboxylate,L-DOPA (3,4-dihydroxy-L-phenylalanine), proteins, carbohydrates,glycoproteins, mucopolysaccharides, other polysaccharides, hydrogels,protein-based binders such as fibrin glues and mussel-derived adhesiveproteins, and any other suitable sub stance.

In some embodiments, the removable distal end forms the distal endopening via mechanical means such as via cutting or tearing the distalend of the tubular member with scissors and/or a blade.

In some embodiments, the particulate bone material can be loaded intothe device from the proximal end opening of the tubular member via afunnel 41 or other loading instrument, as shown in FIG. 1. The funnelengages the proximal end opening of the tubular member and theparticulate bone material is loaded into the channel of the tubularmember.

The tubular member of the device is configured to slidably engage with aproximal end 43 of a cannula 44, and the proximal end opening andchannel of the tubular member is configured to slidably receive aplunger 46, as shown in FIGS. 4 and 5 for administration of theparticulate bone material to a surgical site once the particulate bonematerial is hydrated via the device. As described below, the device isimmersed in a fluid filled bath 50 to hydrate the particulate bonematerial that is loaded into the tubular member. Once hydrated, theparticulate bone material will be dispensed out of a distal end opening45 of the cannula into a surgical site.

In some embodiments, the proximal end opening of the tubular membercomprises a collar 48 that is configured to engage with the proximal endof the cannula, as shown in FIG. 4. The collar will be flush or restingon a surface of the proximal end of the cannula. In some embodiments,the proximal end of the cannula can include a collar configured toengage with the tubular member. In some embodiments, the collar is arigid funnel. In some embodiments, when the proximal end openingincludes a collar, the collar has a width W3 that is greater than widthW1. In some embodiments, width W3 is from about 0.5 to about 5 inches,from about 1 inch to about 5 inches, from about 1 to about 4 inches,from about 1 to about 3, from about 1 to about 2 inches, from about 2 toabout 5 inches, from about 2 to about 4 inches, from about 2 to about 3inches, from about 3 to about 5 inches or from about 4 to about 5inches. In some embodiments, width W3 can be from about 0.5, 0.6, 0.7,0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2,2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7,3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9 to about 5inches.

In some embodiments, the tubular member comprises a mesh and/or a straw.In some embodiments, the mesh can be made from a natural and/orsynthetic material.

In some embodiments, the tubular member is moldable or flexible. In someembodiments, the tubular member is flexible and elastic, which allowsthe tubular member to be kneaded while in the fluid filled bath. In thisembodiment, if the tubular member is compressed, any air containedwithin the tubular member will be pushed out through the pores. When thetubular member elastically returns to its original shape, the tubularmember will draw in fluid, thereby hydrating the contained bonematerial. In some embodiments, the tubular member has a modulus ofelasticity from about from about 1×−10² to about 6×10⁵ dynes/cm², or2×10⁴ to about 5×10⁵ dynes/cm², or 5×10⁴ to about 5×10⁵ dynes/cm².

In some embodiments, the tubular member is flexible but relativelyinelastic, such that the tubular member does not return to its originalshape easily. In this embodiment, the tubular member being flexible butrelatively inelastic would allow the tubular member to be hydrated in asmaller fluid filled bath by allowing the tubular member to be coiled onitself, as well as would allow less manipulation by the surgeon whenpositioning in-situ before dispensing the bone material.

In some embodiments, the tubular member can be rigid. A rigid tubularmember facilitates easy attachment of a delivery tip (not shown) ontothe tubular member, allows the tubular member to be easily moved throughthe funnel and/or allows the device to be used without a deliveryinstrument. In some embodiments, portions of the tubular member can beflexible, while other portions can be rigid.

In some embodiments, the tubular member can be made from a material thatis flexible when dry but becomes rigid when hydrated. In thisembodiment, the transition of the material from flexible to rigid canoccur over a period of time, such as after the device is immersed in thefluid filled bath. In some embodiments, the tubular member can initiallybe rigid and then can become softer and more flexible as the tubularmember is soaked.

As described above, the device is immersed in a fluid filled bath 50 tohydrate the particulate bone material. In some embodiments, the deviceis fully immersed in the fluid filled bath for an amount of time. Insome embodiments, the device is fully immersed in the fluid filled bathfrom about 10 seconds to about 24 hours, depending on the composition ofthe particulate bone material and the fluid. In some embodiments, thedevice is fully immersed in the fluid filled bath from about 10, 15, 20,25, 30, 35, 40, 45, 50, 55 seconds, 1, 2, 4, 6, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54,56, 58, 60 minutes, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23 to about 24 hours.

In some embodiments, the fluid can be blood, bone marrow aspirate,mesenchymal stem cells, sterile water, dextrose, other sugars includingbut not limited to sucrose, fructose, glucose, lactated ringer's,polyols including, but not limited to, mannitol, xylitol, sorbitol,maltitol, lactitol, polysaccharides including, but not limited to,native or pre-gelatinized starch, maltodextrins, cyclodextrins, mineralcompounds including, but not limited to, dicalcium or tricalciumphosphate, either dihydrate or anhydrous, cellulose derivativesincluding, but not limited to, microcrystalline cellulose, lactoseseither monohydrates thereof or anhydrous, as well as their mixtures suchas dicalcium phosphate dihydrate, mannitol, pre-gelatinized maizestarch, microcrystalline cellulose and their mixtures, water and/or NaCl(saline). In some embodiments, the saline is 0.90% saline, 0.45% salineor phosphate buffered saline. In some embodiments, other fluids can beused for example, D5W (dextrose in 5% water), D5NS (dextrose in 5% waterand normal saline) and D5W/½NS (D5W and ½ normal saline), lactatedRinger solution or the like.

In some embodiments, the particulate bone material is in a powder or awet form and has a particle size of 250 microns or less. In someembodiments, the particulate bone material is demineralized bone (DBM).

In some embodiments, the tubular member of the device can be pre-packedwith the particulate bone material from a manufacturer with the proximalend and the distal end of the tubular member sealed. The ends can thenbe cut prior to use and administration.

Referring to FIGS. 6-9, a device 200, similar to device 20 above, isprovided for hydrating particulate bone material. The device isconfigured to hydrate the particulate bone material beforeadministration of the particulate bone material to a surgical site. Thehydrated particulate bone material is fully contained in the device andafter hydration, the device ejects the particulate bone material at thesurgical site.

The device includes a tubular member 202, similar to tubular member 24,having an interior surface 204 and an exterior surface 206, as shown inFIG. 6. The interior surface defines a channel 208 and is configured toreceive the particulate bone material and a hydration fluid 30. Theexterior surface of the tubular member includes a plurality of pores 210configured to allow the hydration fluid to flow into the interiorsurface of the tubular member and hydrate the particulate bone material.The plurality of pores are smaller in size than the particulate bonematerial. In some embodiments, the plurality of pores have a pore sizefrom about 10 to about 100 microns, from about 20 to about 80 microns,or from about 40 to about 60 microns. In some embodiments, the pluralityof pores can have a pore size from about 10, 12, 14, 16, 18, 20, 22, 24,26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60,62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96,98 to about 100 microns. In some embodiments, the plurality of pores canbe the same or various sizes throughout the tubular member, theplurality of pores can be larger when disposed at a distal end, can beuniform throughout, as shown in FIG. 6 or can be larger in distinctzones on the exterior surface of the tubular member. In someembodiments, the tubular member is mesh and/or a straw, as describedabove with regard to device 20. In some embodiments, the tubular membercan be flexible.

The tubular member comprises a proximal end 212 defining a proximal endopening 214, a distal end 216 defining a distal end opening 218 and alongitudinal axis BB disposed therebetween. The proximal end opening isconfigured to receive the particulate bone material and the distal endopening is configured to dispense the particulate bone material. In someembodiments, a removable distal end 219 forms the distal end opening viamechanical means such as via cutting or tearing the distal end of thetubular member with scissors and/or a blade.

The tubular member can have a length L2, a width W4 at the proximal endand a width W5 at the distal end. The length L2 can be from about 1 inchto about 20 inches, from about 1 to about 15 inches, from about 1 toabout 10 inches, from about 1 to about 5 inches, from about 5 to about20 inches, from about 5 to about 15 inches, from about 5 to about 10inches, from about 10 to about 20 inches, from about 10 to about 15inches, or from about 15 to about 20 inches. In some embodiments, thelength L2 can be from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19 to about 20 inches.

In some embodiments, widths W4 and W5 can be from about 0.5 to about 5inches, from about 1 inch to about 5 inches, from about 1 to about 4inches, from about 1 to about 3, from about 1 to about 2 inches, fromabout 2 to about 5 inches, from about 2 to about 4 inches, from about 2to about 3 inches, from about 3 to about 5 inches or from about 4 toabout 5 inches. In some embodiments, widths W4 and W5 can be from about0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9,2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4,3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9to about 5 inches. In some embodiments, widths W4 and W5 can be the sameor different sizes.

The interior surface of the tubular member at the proximal end includesthreading 220 that engages with a threaded outer surface 224 of aplunger 222, as shown in FIGS. 7 and 9. In some embodiments, thethreading can be angled, horizontal or partially threaded. Engagement ofthe tubular member and the plunger facilitates dispensing of theparticulate bone material.

The tubular member includes a valve 226 and a port 228 that isconfigured to receive a syringe 230 having a barrel 235, as shown inFIGS. 8 and 9. For example, a distal end or tip 232 of the syringeengages with the port 228 and a user can move a syringe plunger 234 inan upward direction to draw air and/or fluid out of the tubular memberand into the syringe barrel such that a vacuum is formed. Negativepressure will be created in the tubular member. In some embodiments, thevalve can be a one-way valve, such that any vacuum introduced wouldremain after the syringe is removed.

The port has a length L3 and a width W6. In some embodiments, the lengthL3 is from about 0.5 to about 5 inches, from about 1 to about 4 inches,or from about 2 to about 3 inches. In some embodiments, the length L3 isfrom about 0.5, 1, 2, 3, 4 to about 5 inches. In some embodiments, theport is disposed perpendicular to the tubular member and has an angleα1. In some embodiments, angle α1 is from about 20 to 60 degrees. Insome embodiments, angle α1 is from about 20, 21, 22, 23, 24, 25, 26, 27,28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45,46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 to about 60degrees.

The device is immersed in the fluid filled bath 50 shown in FIG. 3 tohydrate the particulate bone material. In some embodiments, the deviceis fully immersed in the fluid filled bath for an amount of time. Insome embodiments, the device is fully immersed in the fluid filled bathfrom about 10 seconds to about 24 hours, depending on the composition ofthe particulate bone material and the fluid. In some embodiments, thedevice is fully immersed in the fluid filled bath from about 10, 15, 20,25, 30, 35, 40, 45, 50, 55 seconds, 1, 2, 4, 6, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54,56, 58, 60 minutes, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23 to about 24 hours. In some embodiments, whilethe device is immersed in the fluid filled bath, the proximal end or tipof the syringe is attached to the device via engagement with the port.As shown in FIG. 9, the user then moves the syringe plunger in an upwarddirection to create a vacuum to draw fluid from the fluid filled bathinto the tubular member to hydrate the bone material. Negative pressureis then created in the tubular member. The device is then removed fromthe fluid filled bath and the syringe is disengaged from the port. Theplunger is then attached to the proximal end opening of the tubularmember and the plunger is moved in a downward direction to dispense thehydrated particulate bone material out of the distal end opening of thetubular member and into a surgical site. In some embodiments, fluid canbe inserted into the device through the port.

In some embodiments, the tubular member can be packed with the bonematerial under a vacuum such that as the tubular member isopened/cut/placed in the fluid filled bath, the internal vacuum willdraw up the fluid, thus removing the need to draw the fluid into thetubular member externally by using a syringe.

Referring to FIGS. 10-12, a device 300, similar to devices 20 and 200above, is provided for hydrating particulate bone material. The deviceis configured to hydrate the particulate bone material prior to loadingof the particulate bone material into a delivery instrument. Thehydrated particulate bone material is fully contained in the device andis then loaded into a delivery instrument for administration to asurgical site.

The device comprising a tubular member 302, similar to tubular members24 and 202, having an interior surface 304 and an exterior surface 306,as shown in FIG. 11. The interior surface defines a channel 308 and isconfigured to receive the particulate bone material 22 and hydrationfluid 30. The tubular member includes a proximal end 310 defining aproximal end opening 312, a distal end 314 defining a distal end opening316 and a longitudinal axis CC disposed therebetween. In someembodiments, the tubular member comprises a straw.

The proximal end opening is configured to receive the particulate bonematerial and the distal end opening is configured to dispense theparticulate bone material. The proximal end opening is configured toreceive a syringe 318 having a syringe plunger 320, and the distal endopening is configured to receive a cap 322. In some embodiments, thesyringe is a standard or vacuum lock syringe.

The tubular member can have a length L4, a width W6 at the proximal endand a width W7 at the distal end. The length L4 can be from about 1 inchto about 20 inches, from about 1 to about 15 inches, from about 1 toabout 10 inches, from about 1 to about 5 inches, from about 5 to about20 inches, from about 5 to about 15 inches, from about 5 to about 10inches, from about 10 to about 20 inches, from about 10 to about 15inches, or from about 15 to about 20 inches. In some embodiments, thelength L4 can be from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19 to about 20 inches.

In some embodiments, widths W6 and W7 can be from about 0.5 to about 5inches, from about 1 inch to about 5 inches, from about 1 to about 4inches, from about 1 to about 3, from about 1 to about 2 inches, fromabout 2 to about 5 inches, from about 2 to about 4 inches, from about 2to about 3 inches, from about 3 to about 5 inches or from about 4 toabout 5 inches. In some embodiments, widths W6 and W7 can be from about0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9,2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4,3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9to about 5 inches. In some embodiments, widths W6 and W7 can be the sameor different sizes.

The cap includes a plurality of pores 324 configured to allow thehydration fluid to flow into the interior surface of the tubular memberand hydrate the particulate bone material. The plurality of pores aresmaller in size than the particulate bone material. In some embodiments,the plurality of pores have a pore size from about 10 to about 100microns, from about 20 to about 80 microns, or from about 40 to about 60microns. In some embodiments, the plurality of pores can have a poresize from about 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36,38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72,74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98 to about 100 microns.In some embodiments, the plurality of pores can be the same or varioussizes throughout the cap, can be uniform throughout, or can be larger indistinct zones on the cap.

The proximal end opening of the tubular member engages with a cap 326that includes a luer fitting 328 that engages with a distal end 330 ofthe syringe.

Once the proximal end opening of the tubular member engages with the caphaving the luer fitting, the distal end of the syringe is engaged withthe luer fitting. The tubular member at the distal end/cap is immersedin the fluid filled bath 50 shown in FIG. 10. The syringe plunger ismoved in an upward direction to create a vacuum which draws the fluidfrom the bath into the plurality of pores of the cap and up the channelof the tubular member to hydrate the particulate bone material. As shownin FIGS. 11 and 12, the caps are then removed from the ends of thetubular member and the device can then be loaded into a deliveryinstrument so that the hydrated particulate bone material can beadministered to a surgical site.

In some embodiments, components of the device can be fabricated frombiologically acceptable materials suitable for medical applications,including metals, synthetic polymers, ceramics and/or their composites.For example, the components of the device, individually or collectively,can be fabricated from materials such as stainless steel alloys,commercially pure titanium, titanium alloys, Grade 5 titanium,super-elastic titanium alloys, cobalt-chrome alloys, stainless steelalloys, superelastic metallic alloys (e.g., Nitinol, superelasto-plastic metals, such as GUM METAL® manufactured by ToyotaMaterial Incorporated of Japan), ceramics and composites thereof such ascalcium phosphate (e.g., SKELITE′ manufactured by Biologix Inc.),thermoplastics such as polyaryletherketone (PAEK) includingpolyetheretherketone (PEEK), polyetherketoneketone (PEKK) andpolyetherketone (PEK), carbon-PEEK composites, PEEK-BaSO₄ polymericrubbers, polyethylene terephthalate (PET), fabric, silicone,polyurethane, silicone-polyurethane copolymers, polymeric rubbers,polyolefin rubbers, hydrogels, semi-rigid and rigid materials,elastomers, rubbers, thermoplastic elastomers, thermoset elastomers,elastomeric composites, rigid polymers including polyphenylene,polyamide, polyimide, polyetherimide, polyethylene, epoxy, or anycombination thereof.

In some embodiments, lubricants can be added to components of the deviceor can be added to the bone material. In some embodiments, lubricantscan include biological lubricants such as, glycerol, rapeseed, canola,sunflower, soybean, palm oil, coconut oil, sesame seed oil, cottonseedoil, safflower oil, olive oil, almond oil, peanut oil, poppy seed oiland/or castor oil. In some embodiments, the tubular member can include alubricant layer or layers.

Kit

In various embodiments, the kit may include additional parts along withthe device combined together to be used with the particulate bonematerial (e.g., bone graft) and dilators (e.g., wipes, needles,syringes, etc.). The kit may include the device in a first compartment.The second compartment may include the particulate bone material, alongwith a mesh or a vial containing diluent and any other deliveryinstruments (e.g., cannula, plunger, etc.) needed for the localizedimplant delivery. A third compartment may include a funnel, gloves,drapes, wound dressings and other procedural supplies for maintainingsterility of the implanting process, as well as an instruction booklet,which may include a chart that shows how to implant the bone material. Afourth compartment may include additional needles, fasteners, and/orsutures. Each tool may be separately packaged in a plastic pouch that isradiation sterilized. A fifth compartment may include an agent forradiographic imaging. A cover of the kit may include illustrations ofthe implanting procedure and a clear plastic cover may be placed overthe compartments to maintain sterility.

Bone Material

The bone material has a particle size that is greater than the pore sizeof the tubular member when the tubular member is porous. In someembodiments, the tubular member can be non-porous however, the cap canhave a plurality of pores that are smaller than the particle size of thebone material. In this way, the tubular member and/or the cap can allowfluid flow to hydrate the bone material.

In some embodiments, the bone material can be made from natural boneand/or synthetic bone. In various embodiments, the bone material may beparticulated such as, for example, in bone chips, powder or fiber form.In some embodiments, the particulate bone material is in a powder or awet form and has a particle size of 250 microns or less. In someembodiments, the particulate bone material has a particle size of 2, 4,6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40,42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76,78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108,110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136,138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164,166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192,194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220,222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248and/or 250 microns. In some embodiments, the particulate bone materialis demineralized bone (DBM).

If the bone is demineralized, the bone may be made into a particulatebefore, during or after demineralization. In some embodiments, the bonemay be monolithic and may not be a particulate.

The bone may be milled and ground or otherwise processed into particlesof an appropriate size before or after demineralization. The particlesmay be particulate (for example, powder) or fibrous. The terms millingor grinding are not intended to be limited to production of particles ofa specific type and may refer to production of particulate or fibrousparticles. In certain embodiments, the particle size may be greater than25 microns, such as ranging from about 25 to about 250 microns, or fromabout 25 to about 200 microns or from about 25 to about 150 microns.

After grinding, the bone particles may be sieved to select thoseparticles of a desired size. In certain embodiments, the particles maybe sieved though a 25 micron sieve, a 50 micron sieve, a 75 micronsieve, a 100 micron sieve, a 125 micron sieve, a 150 micron sieve, a 175micron sieve and/or a 200 micron sieve.

In some embodiments, the bone material comprises DBM and/or mineralizedbone. In some embodiments, the size of the bone material is less than25, 50, 75, 100, 125, 150, 175, 200 or 250 microns.

Following shaving, milling or other technique whereby they are obtained,the bone material is subjected to demineralization in order to reduceits inorganic content to a very low level, in some embodiments, to notmore than about 5% by weight of residual calcium and to not more thanabout 1% by weight of residual calcium. Demineralization of the bonematerial ordinarily results in its contraction to some extent.

Bone used in the methods described herein may be autograft, allograft,or xenograft. In various embodiments, the bone may be cortical bone,cancellous bone, or cortico-cancellous bone. While specific discussionis made herein to demineralized bone matrix, bone matrix treated inaccordance with the teachings herein may be non-demineralized,demineralized, partially demineralized, or surface demineralized. Thisdiscussion applies to demineralized, partially demineralized, andsurface demineralized bone matrix. In one embodiment, the demineralizedbone is sourced from bovine or human bone. In another embodiment,demineralized bone is sourced from human bone. In one embodiment, thedemineralized bone is sourced from the patient's own bone (autogenousbone). In another embodiment, the demineralized bone is sourced from adifferent animal (including a cadaver) of the same species (allograftbone).

Any suitable manner of demineralizing the bone may be used.Demineralization of the bone material can be conducted in accordancewith known conventional procedures. For example, in a preferreddemineralization procedure, the bone materials useful for theimplantable composition of this application are subjected to an aciddemineralization step that is followed by a defatting/disinfecting step.The bone material is immersed in acid over time to effect itsdemineralization. Acids which can be employed in this step includeinorganic acids such as hydrochloric acid and organic acids such asperacetic acid, acetic acid, citric acid, or propionic acid. The depthof demineralization into the bone surface can be controlled by adjustingthe treatment time, temperature of the demineralizing solution,concentration of the demineralizing solution, agitation intensity duringtreatment, and other applied forces such as vacuum, centrifuge,pressure, and other factors such as known to those skilled in the art,Thus, in various embodiments, the bone material may be fullydemineralized, partially demineralized, or surface demineralized.

After acid treatment, the bone is rinsed with sterile water forinjection, buffered with a buffering agent to a final predetermined andthen finally rinsed with water for injection to remove residual amountsof acid and buffering agent or washed with water to remove residual acidand thereby raise the pH. Following demineralization, the bone materialis immersed in solution to effect its defatting. Adefatting/disinfectant solution is an aqueous solution of ethanol, theethanol being a good solvent for lipids and the water being a goodhydrophilic carrier to enable the solution to penetrate more deeply intothe bone. The aqueous ethanol solution also disinfects the bone bykilling vegetative microorganisms and viruses. Ordinarily at least about10 to 40 weight percent by weight of water (i.e., about 60 to 90 weightpercent of defatting agent such as alcohol) should be present in thedefatting/disinfecting solution to produce optimal lipid removal anddisinfection within the shortest period of time. The concentration rangeof the defatting solution is from about 60 to 85 weight percent alcoholor about 70 weight percent alcohol.

Further in accordance with this application, the DBM material can beused immediately for preparation of the bone implant or it can be storedunder aseptic conditions, advantageously in a critical point dried stateprior to such preparation. In one embodiment, the bone material canretain some of its original mineral content such that the composition isrendered capable of being imaged utilizing radiographic techniques.

In various embodiments, this application also provides bone matrixcompositions comprising critical point drying (CPD) fibers. DBM includesthe collagen matrix of the bone together with acid insoluble proteinsincluding bone morphogenic proteins (BMPs) and other growth factors. Itcan be formulated for use as granules, gels, sponge material or puttyand can be freeze-dried for storage, Sterilization procedures used toprotect from disease transmission may reduce the activity of beneficialgrowth factors in the DBM. DBM provides an initial osteoconductivematrix and exhibits a degree of osteoinductive potential, inducing theinfiltration and differentiation of osteoprogenitor cells from thesurrounding tissues.

DBM preparations have been used for many years in orthopedic medicine topromote the formation of bone. For example, DBM has found use in therepair of fractures, in the fusion of vertebrae, in joint replacementsurgery, and in treating bone destruction due to underlying disease suchas rheumatoid arthritis, DBM is thought to promote bone formation invivo by osteoconductive and osteoinductive processes. The osteoinductiveeffect of implanted DBM compositions is thought to result from thepresence of active growth factors present on the isolated collagen-basedmatrix. These factors include members of the TGF-β, IGF, and BMP proteinfamilies. Particular examples of osteoinductive factors include TGF-β,IGF-1, BMP-2, BMP-7, parathyroid hormone (PTH), and angiogenic factors.Other osteoinductive factors such as osteocalcin and osteopontin arealso likely to be present in DBM preparations as well. There are alsolikely to be other unnamed or undiscovered osteoinductive factorspresent in DBM.

In various embodiments, the DBM provided in this application can beprepared from elongated bone fibers which have been subjected tocritical point drying (CPD). The elongated CPD bone fibers employed inthis application are generally characterized as having relatively highaverage length to average width ratios, also known as the aspect ratio.In various embodiments, the aspect ratio of the elongated bone fibers isat least from about 50:1 to at least about 1000:1. Such elongated bonefibers can be readily obtained by any one of several methods, forexample, by milling or shaving the surface of an entire bone orrelatively large section of bone.

In other embodiments, the length of the fibers can be at least about 3.5cm and average width from about 2.0 mm to about 1 cm. In variousembodiments, the average length of the elongated fibers can be fromabout 3.5 cm to about 6.0 cm and the average width from about 20 mm toabout 1 cm. In other embodiments, the elongated fibers can have anaverage length from about 4.0 cm to about 6.0 cm and an average widthfrom about 20 mm to about 1 cm.

In yet other embodiments, the diameter or average width of the elongatedfibers is, for example, not more than about 1.00 cm, not more than 0.5cm or not more than about 0.01 cm. In still other embodiments, thediameter or average width of the fibers can be from about 0.01 cm toabout 0.4 cm or from about 0.02 cm to about 0.3 cm.

In another embodiment, the aspect ratio of the fibers can be from about50:1 to about 950:1, from about 50:1 to about 750:1, from about 50:1 toabout 500:1, from about 50:1 to about 250:1; or from about 50:1 to about100:1. Fibers according to this disclosure can have an aspect ratio fromabout 50:1 to about 1000:1, from about 50:1 to about 950:1, from about50:1 to about 750:1, from about 50:1 to about 600:1, from about 50:1 toabout 350:1, from about 50:1 to about 200:1, from about 50:1 to about100:1, or from about 50:1 to about 75:1.

In some embodiments, the chips to fibers ratio is about 90:10, 80:20,75:25, 70:30, 60:40, 50:50, 40:60, 30:70, 25:75, 20:80 and/or 10:90, Invarious embodiments, a surface demineralized chips to fibers ratio isabout 90:10, 80:20, 75:25, 70:30, 60:40, 50:50, 40:60, 30:70, 25:75,20:80 and/or 10:90. In some embodiments, a surface demineralized chipsto fully demineralized fibers ratio is about 90:10, 80:20, 75:25, 70:30,60:40, 50:50, 40:60, 30:70, 25:75, 20:80 and/or 10:90.

In some embodiments, the DBM fibers have a thickness of about 0.5-4 mm.In various embodiments, the DBM fibers have a thickness of about 0.5,0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5 and/or 4 mm. In variousembodiments, the ratio of DBM fibers to DBM powder is about 40:60 toabout 90:10 W/W, W/V or V/V. In some embodiments, the ratio ofmineralized bone fibers to DBM powder is about 25:75 to about 75:25 W/W,W/V or V/V. In various embodiments, the bone implant comprises DBMfibers and mineralized fibers in a ratio of 40:60 to about 90:10 W/W,W/V or V/V. In some embodiments, the DBM fibers to DBM powder ratio,mineralized bone fibers to DBM powder ratio and/or the DBM fibers andmineralized fibers ratio is from 5:95 to about 95:5 W/W, W/V or V/V. Insome embodiments, the DBM fibers to DBM powder ratio, mineralized bonefibers to DBM powder ratio and/or the DBM fibers and mineralized fibersratio is 5:95, 10:90, 15:85, 20:80, 25:75, 30:70, 35:65, 40:60, 45:55,50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10 and/or95:5 W/W, W/V or VN.

In some embodiments, the bone material comprises demineralized bonematerial comprising demineralized bone, fibers, powder, chips,triangular prisms, spheres, cubes, cylinders, shards or other shapeshaving irregular or random geometries. These can include, for example,“substantially demineralized,” “partially demineralized,” or “fullydemineralized” cortical and/or cancellous bone. These also includesurface demineralization, where the surface of the bone construct issubstantially demineralized, partially demineralized, or fullydemineralized, yet the body of the bone construct is fully mineralized.

In various embodiments, the bone material comprises fully DBM fibers andsurface demineralized bone chips. In some embodiments, the ratio offully DBM fibers to surface demineralized bone chips is from 5:95 toabout 95:5 fibers to chips. In some embodiments, the ratio of fully DBMfibers to surface demineralized bone chips is 5:95, 10:90, 15:85, 20:80,25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30,75:25, 80:20, 85:15, 90:10 and/or 95:5 fibers to chips. In variousembodiments, the fully DBM fibers have a thickness of about 0.5-4 mm. Invarious embodiments, the fully DBM fibers have a thickness of about 0.5,0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5 and/or 4 mm.

In various embodiments, the fibers and/or the powder is surface DBM. Insome embodiments, the fibers and/or the powder is surface DBM corticalallograft. In various embodiments, surface demineralization involvessurface demineralization to at least a certain depth. For example, thesurface demineralization of the allograft can be from about 0.25 mm, 0.5mm, 1 mm, 1.5 mm, 2.0 mm, 2.5 mm, 3.0 mm. 3.5 mm, 4 mm, 4.5 mm, to about5 mm. The edges of the bone fibers and/or powder may further be machinedinto any shape or to include features such as grooves, protrusions,indentations, etc., to help improve fit and limit any movement ormicromotion to help fusion and/or osteoinduction to occur.

To prepare the osteogenic DBM, a quantity of fibers is combined with abiocompatible carrier to provide a demineralized bone matrix.

DBM typically is dried, for example via lyophilization or solventdrying, to store and maintain the DBM in active condition forimplantation. Moreover, each of these processes is thought to reduce theoverall surface area structure of bone. As may be appreciated, thestructural damage of the exterior surface reduces the overall surfacearea. Physical alterations to the surface and reduction in surface areacan affect cell attachment, mobility, proliferation, anddifferentiation. The surface's affinity for growth factors and releasekinetics of growth factors from the surface may also be altered.

Accordingly, in some embodiments, methods for drying bone to store andmaintain the bone in active condition for implantation that maintains orincreases the surface area of the bone are provided. In one embodiment,the bone matrix is treated using a critical point drying technique,thereby reducing destruction of the surface of the bone. While specificdescription is made to critical point drying, it is to be appreciatedthat, in alternative embodiments, super critical point treatment may beused. In various embodiments utilizing CPD, a percentage of collagenfibrils on the surface of the bone are non-denatured after drying to aresidual moisture content of approximately 15% or less. In someembodiments, after drying, the bone matrix has a residual moisturecontent of approximately 8% or less. In some embodiments, after drying,the bone matrix has a residual moisture content of approximately 6% orless. In some embodiments, after drying, the bone matrix has a residualmoisture content of approximately 3% or less.

Evaporative drying and freeze drying of specimens can cause deformationand collapse of surface structures, leading to a decrease in surfacearea. Without wishing to be bound by a particular theory, thisdeformation and structure is thought to occur because as a substancecrosses the boundary from liquid to gas, the substance volatilizes suchthat the volume of the liquid decreases. As this happens, surfacetension at the solid-liquid interface pulls against any structures towhich the liquid is attached. Delicate surface structures tend to bebroken apart by this surface tension. Such damage may be caused by theeffects of surface tension on the liquid/gas interface. Critical pointdrying is a technique that avoids effects of surface tension on theliquid/gas interface by substantially preventing a liquid/gas interfacefrom developing. Critical point or supercritical drying does not crossany phase boundary, instead passing through the supercritical region,where the distinction between gas and liquid ceases to apply. As aresult, materials dehydrated using critical point drying are not exposedto damaging surface tension forces. When the critical point of theliquid is reached, it is possible to pass from liquid to gas withoutabrupt change in state. Critical point drying can be used with bonematrices to phase change from liquid to dry gas without the effects ofsurface tension. Accordingly, bone dehydrated using critical pointdrying can retain or increase at least some of the surface structure andtherefore the surface area.

In some embodiments, critical point drying is carried out using carbondioxide. However, other mediums such as Freon, including Freon 13(chlorotrifluoromethane), may be used. Generally, fluids suitable forsupercritical drying include carbon dioxide (critical point 304.25 K at7.39 MPa or 31.1° C. at 1072 psi or 31.2° C. and 73.8 bar) and Freon(about 300 K at 3.5-4 MPa or 25 to 30° C. at 500-600 psi). Nitrous oxidehas similar physical behavior to carbon dioxide, but is a powerfuloxidizer in its supercritical state. Supercritical water is also apowerful oxidizer, partly because its critical point occurs at such ahigh temperature (374° C.) and pressure (3212 psi/647K and 22.064 MPa).

In some embodiments, the bone may be pretreated to remove water prior tocritical point drying. Thus, in accordance with one embodiment, bonematrix is dried using carbon dioxide in (or above) its critical pointstatus. After demineralization, bone matrix samples (in water) may bedehydrated to remove residual water content. Such dehydration may be,for example, through a series of graded ethanol solutions (for example,20%, 50%, 70%, 80%, 90%, 95%, 100% ethanol in deionized water). In someembodiments, penetrating the tissue with a graded series of ethanolsolutions or alcohols may be accomplished in an automated fashion. Forexample, pressure and vacuum could be used to accelerate penetrationinto the tissue.

Mesh Formulations

In some embodiments, the tubular member comprises a mesh and/or a straw.In some embodiments, the mesh can be made from a natural and/orsynthetic material such as, for example, poly(lactide-co-glycolide)(PLGA), polylactide (PLA), polyglycolide (PGA), D-lactide, D,L-lactide,L-lactide, D,L-lactide-co-ε-caprolactone,D,L-lactide-co-glycolide-co-ε-caprolactone, L-lactide-co-ε-caprolactone,polydioxanone (PDO), allogeneic collagen, xenogenic collagen, metalssuch as titanium/titanium alloys, TiNi (shape memory/super elastic),aluminum oxide, platinum/platinum alloys, stainless steels, and othermetal alloys known to be useful for medical devices, pyrolytic carbon,silver or glassy carbon; polymers such as polyurethanes, polycarbonates,silicone elastomers, polyolefins including polyethylenes orpolypropylenes (such as found in hernia mesh substrates and suturematerials), polyvinyl chlorides, polyethers, polyesters, nylons,polyvinyl pyrrolidones, polyacrylates and polymethacrylates such aspolymethylmethacrylate (PMMA), n-Butyl cyanoacrylate, polyvinylalcohols, polyisoprenes, rubber, cellulosics, polyvinylidene fluoride(PVDF), polytetrafluoroethylene, ethylene tetrafluoroethylene copolymer(ETFE), acrylonitrile butadiene ethylene, polyamide, polyimide, styreneacrylonitrile, and the like; minerals or ceramics such as hydroxapatite;human or animal protein or tissue such as bone, skin, teeth, collagen,laminin, elastin or fibrin; organic materials such as wood, cellulose,or compressed carbon; and other materials such as glass or a combinationthereof.

The mesh can be made from yarn that is monofilament or multi filament,and the mesh can be fabricated using knitting, weaving, non-woven, suchas felted or point-bonded, or with additive manufacturing methods (e.g.,3D printing). The mesh can be made of yarn that is monofilament ormultifilament, and the yarn can be knitted, woven, non-woven shapememory, felted, point-bonded, additive manufactured, such as 3-D printedor a combination thereof. A weave pattern can be selected to impartflexibility and stretchable characteristics to the mesh.

The mesh can have a weave density of from about 8 to about 400filaments, such as fibers per inch. The mesh can have a weave densityfrom about 8 to about 375 filaments fibers per inch, from about 8 toabout 350 fibers per inch, from about 8 to about 300 fibers per inch,from about 8 to about 250 fibers per inch, from about 8 to about 200fibers per inch, from about 20 to about 350 fibers per inch, from about20 to about 300 fibers per inch, from about 20 to about 250 fibers perinch, from about 20 to about 200 fibers per inch, from about 50 to about350 fibers per inch, from about 50 to about 300 fibers per inch, fromabout 50 to about 250 fibers per inch, from about 50 to about 200 fibersper inch, from about 100 to about 350 fibers per inch, from about 100 toabout 300 fibers per inch, from about 100 to about 250 fibers per inch,or from about 100 to about 200 fibers per inch. The mesh can have aweave density from about 8, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60,65, 70, 75, 80, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140,145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210,215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280,285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345 to about350 fibers per inch.

The average molecular weight of the polymer used to make the mesh can befrom about 1,000 to about 10,000,000; or about 1,000 to about 1,000,000;or about 5,000 to about 500,000; or about 10,000 to about 100,000; orabout 20,000 to 50,000 g/mol. In some embodiments, the molecular weightof the polymer is 1,000, 2,000, 3,000, 4,000, 5,000, 6,000, 7,000,8,000, 9,000, 10,000, 15,000, 20,000, 25,000, 30,000, 35,000, 40,000,45,000, 50,000, 55,000, 60,000, 65,000, 70,000, 75,000, 80,000, 85,000,90,000, 95,000, 100,000, 125,000, 150,000, 175,000, 200,000, 225,000,250,000, 275,000, 300,000, 325,000, 350,000, 375,000, 400,000, 425,000,450,000, 475,000, 500,000, 525,000, 550,000, 575,000, 600,000, 625,000,650,000, 675,000, 700,000, 725,000, 750,000, 775,000, 800,000, 825,000,850,000, 875,000, 900,000, 925,000, 950,000, 975,000 and/or 1,000,000Daltons.

The mesh may have varying degrees of permeability. It may be permeable,semi-permeable, or non-permeable throughout, or in discrete locations.Permeability may be with respect to cells, to liquids, to proteins, togrowth factors, to bone morphogenetic proteins, or other substances. Themesh may be 1 to about 30% permeable, from about 30 to about 70%permeable, or from about 70 to about 95% permeable. The mesh may be 1,5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90,95, 96, 97, 98, or 99% permeable.

In some embodiments, the mesh can be made from threads and can have apredetermined thickness of about 0.01 mm to about 2.0 mm, about 0.05 mmto about 1.0 mm, or about 0.1 to about 0.5 mm. The thickness of thethreads may be uniform along the length of each thread, or varied acrossthe length of each thread. In some embodiments, some threads have agreater thickness than other threads. The threads may be sized to allowfor customizable pore sizes between the threads.

Suitable adhesives for use for closing the mesh material may include,for example, cyanoacrylates (such as histoacryl, B Braun, which isn-butyl-2 cyanoacrylate; or Dermabond, which is 2-octylcyanoacrylate);epoxy-based compounds, dental resin sealants, dental resin cements,glass ionomer cements, polymethyl methacrylate,gelatin-resorcinol-formaldehyde glues, collagen-based glues, inorganicbonding agents such as zinc phosphate, magnesium phosphate or otherphosphate-based cements, zinc carboxylate, L-DOPA(3,4-dihydroxy-L-phenylalanine), proteins, carbohydrates, glycoproteins,mucopolysaccharides, other polysaccharides, hydrogels, protein-basedbinders such as fibrin glues and mussel-derived adhesive proteins, andany other suitable substance. Adhesives may be selected for use based ontheir bonding time; for example, in some circumstances, a temporaryadhesive may be desirable, while in other circumstances a permanentadhesive may be desired. In some embodiments, the mesh material can beclosed via heat sealing or sonic welding techniques.

In accordance with some embodiments, the particulate bone material to beloaded in the tubular member may be supplemented, further treated, orchemically modified with one or more bioactive agents or bioactivecompounds. Bioactive agent or bioactive compound, as used herein, refersto a compound or entity that alters, inhibits, activates, or otherwiseaffects biological or chemical events. For example, bioactive agents mayinclude, but are not limited to, osteogenic or chondrogenic proteins orpeptides; DBM powder; collagen, insoluble collagen derivatives, etc.,and soluble solids and/or liquids dissolved therein; anti-AIDSsubstances; anti-cancer substances; antimicrobials and/or antibioticssuch as erythromycin, bacitracin, neomycin, penicillin, polymycin B,tetracyclines, biomycin, chloromycetin, and streptomycins, cefazolin,ampicillin, azactam, tobramycin, clindamycin and gentamycin, etc.;immunosuppressants; anti-viral substances such as substances effectiveagainst hepatitis; enzyme inhibitors; hormones; neurotoxins; opioids;hypnotics; anti-histamines; lubricants; tranquilizers; anti-convulsants;muscle relaxants and anti-Parkinson substances; anti-spasmodics andmuscle contractants including channel blockers; miotics andanti-cholinergics; anti-glaucoma compounds; anti-parasite and/oranti-protozoal compounds; modulators of cell-extracellular matrixinteractions including cell growth inhibitors and antiadhesionmolecules; vasodilating agents; inhibitors of DNA, RNA, or proteinsynthesis; anti-hypertensives; analgesics; anti-pyretics; steroidal andnon-steroidal anti-inflammatory agents; anti-angiogenic factors;angiogenic factors and polymeric carriers containing such factors;anti-secretory factors; anticoagulants and/or antithrombotic agents;local anesthetics; ophthalmics; prostaglandins; anti-depressants;anti-psychotic substances; anti-emetics; imaging agents;biocidal/biostatic sugars such as dextran, glucose, etc.; amino acids;peptides; vitamins; inorganic elements; co-factors for proteinsynthesis; endocrine tissue or tissue fragments; synthesizers; enzymessuch as alkaline phosphatase, collagenase, peptidases, oxidases and thelike; polymer cell scaffolds with parenchymal cells; collagen lattices;antigenic agents; cytoskeletal agents; cartilage fragments; living cellssuch as chondrocytes, bone marrow cells, mesenchymal stem cells; naturalextracts; genetically engineered living cells or otherwise modifiedliving cells; expanded or cultured cells; DNA delivered by plasmid,viral vectors, or other member; tissue transplants; autogenous tissuessuch as blood, serum, soft tissue, bone marrow, or the like;bioadhesives; bone morphogenetic proteins (BMPs including BMP-2);osteoinductive factor (IFO); fibronectin (FN); endothelial cell growthfactor (ECGF); vascular endothelial growth factor (VEGF); cementumattachment extracts (CAE); ketanserin; human growth hormone (HGH);animal growth hormones; epidermal growth factor (EGF); interleukins, forexample, interleukin-1 (IL-1), interleukin-2 (IL-2); human alphathrombin; transforming growth factor (TGF-beta); insulin-like growthfactors (IGF-1, IGF-2); parathyroid hormone (PTH); platelet derivedgrowth factors (PDGF); fibroblast growth factors (FGF, BFGF, etc.);periodontal ligament chemotactic factor (PDLGF); enamel matrix proteins;growth and differentiation factors (GDF); hedgehog family of proteins;protein receptor molecules; small peptides derived from growth factorsabove; bone promoters; cytokines; somatotropin; bone digesters;antitumor agents; cellular attractants and attachment agents;immuno-suppressants; permeation enhancers, for example, fatty acidesters such as laureate, myristate and stearate monoesters ofpolyethylene glycol, enamine derivatives, alpha-keto aldehydes; andnucleic acids.

In certain embodiments, the bioactive agent may be a drug. In someembodiments, the bioactive agent may be a growth factor, cytokine,extracellular matrix molecule, or a fragment or derivative thereof, forexample, a protein or peptide sequence such as RGD.

The material may have functional characteristics. Alternatively, othermaterials having functional characteristics may be incorporated into themesh material. Functional characteristics may include radiopacity,bacteriocidity, source for released materials, tackiness, etc. Suchcharacteristics may be imparted substantially throughout the meshmaterial and/or mesh body or at only certain positions or portions ofthe mesh material and/or mesh body.

Suitable radiopaque materials that can be added to the particulate bonematerial include, for example, ceramics, mineralized bone,ceramics/calcium phosphates/calcium sulfates, metal particles, fibers,and iodinated polymer (see, for example, WO/2007/143698). Suitablebacteriocidal materials may include, for example, trace metallicelements. In some embodiments, trace metallic elements may alsoencourage bone growth.

Methods

A method of hydrating particulate bone material is provided. The devicesand particulate bone material used in this method can be found in FIGS.1-12. The method can be employed with various delivery instrument and ina surgical treatment with a patient in a prone or supine position,and/or employ various surgical approaches to the spine, includinganterior, posterior, posterior mid-line, direct lateral, and/orantero-lateral approaches, and in other body regions. The method mayalso be employed with procedures for treating the lumbar, cervical,thoracic, sacral and pelvic regions of a spinal column. The method mayalso be used on animals, bone models and other non-living substrates,such as, for example, in training, testing and demonstration.

The method comprises loading a device for hydrating the particulate bonematerial, the device comprising a tubular member having an interiorsurface and an exterior surface, the interior surface configured toreceive the particulate bone material and a hydration fluid, theexterior surface having a plurality of pores configured to allow thehydration fluid to flow into the interior surface of the tubular memberand hydrate the particulate bone material, the plurality of pores beingsmaller in size than the particulate bone material; immersing the devicein a fluid filled bath; and engaging the device with a cannula and aplunger to dispense the particulate bone material to the surgical site.

In some embodiments, the proximal end opening of the tubular membercomprises a collar configured to engage the cannula, or a proximal endof the cannula comprises a collar configured to engage the tubularmember.

In some embodiments, the tubular member comprises a removable distal endconfigured to form a distal end opening to dispense the particulate bonematerial.

The bone material may be used in a minimally invasive procedure viaplacement through a small incision, via delivery through the dilators,or other means. The size and shape may be designed with restrictions ondelivery conditions. For example, the bone material may bepercutaneously delivered to the surgical site, and in some cases, thesurgical site is the posterior spine.

In some embodiments, the bone material may be used in healing vertebralcompression fractures, interbody fusion, minimally invasive procedures,posterolateral fusion, correction of adult or pediatric scoliosis,treating long bone defects, osteochondral defects, ridge augmentation(dental/craniomaxillofacial, e.g. edentulous patients), beneath traumaplates, tibial plateau defects, filling bone cysts, wound healing,around trauma, contouring (cosmetic/plastic/reconstructive surgery), andothers.

Generally, the bone material may be applied to a pre-existing defect, toa created channel, or to a modified defect. Thus, for example, a channelmay be formed in a bone, or a pre-existing defect may be cut to form achannel, for receipt of the bone material. The bone material may beconfigured to match the channel or defect. In some embodiments, theconfiguration of bone material may be chosen to match the channel. Inother embodiments, the channel may be created, or the defect expanded oraltered, to reflect a configuration of the bone material. The bonematerial may be placed in the defect or channel and, optionally, coupledusing attachment mechanisms.

Although the invention has been described with reference to embodiments,persons skilled in the art will recognize that changes may be made inform and detail without departing from the spirit and scope of theinvention.

1. A device for hydrating particulate bone material, the devicecomprising a tubular member having an interior surface and an exteriorsurface, the interior surface configured to receive the particulate bonematerial and a hydration fluid, the exterior surface having a pluralityof pores configured to allow the hydration fluid to flow into theinterior surface of the tubular member and hydrate the particulate bonematerial, the plurality of pores being smaller in size than theparticulate bone material, wherein the plurality of pores have a poresize from about 10 to about 100 microns.
 2. The device of claim 1,wherein (i) the tubular member comprises a proximal end openingconfigured to receive the particulate bone material; (ii) the tubularmember comprises a distal end opening configured to dispense theparticulate bone material; (iii) or a combination thereof.
 3. The deviceof claim 1, wherein the tubular member comprises a removable distal endconfigured to form a distal end opening to dispense the particulate bonematerial.
 4. The device of claim 2, wherein the tubular member isconfigured to slidably engage a cannula and the proximal end opening ofthe tubular member is configured to slidably receive a plunger.
 5. Thedevice of claim 4, wherein the proximal end opening of the tubularmember comprises a collar configured to engage the cannula, or aproximal end of the cannula comprises a collar configured to engage thetubular member.
 6. The device of claim 1, wherein the tubular membercomprises a mesh or a straw.
 7. The device of claim 1, wherein thetubular member is moldable or flexible.
 8. The device of claim 5,wherein the collar is a rigid funnel.
 9. The device of claim 1, whereinthe plurality of pores have a pore size from about 10 to about 100microns.
 10. The device of claim 1, wherein the tubular member comprisesa one-way valve.
 11. The device of claim 10, wherein the tubular membercomprises a port configured to receive a syringe.
 12. The device ofclaim 11, wherein the port is disposed perpendicular to the tubularmember.
 13. The device of claim 10, wherein the interior surface of thetubular member at a proximal end comprises threading to engage with athreaded outer surface of a plunger.
 14. The device of claim 1, wherein(i) the particulate bone material is in a powder or a wet form; (ii) theparticulate bone material has a particle size of 250 microns or less; or(iii) the particulate bone material is demineralized bone (DBM).
 15. Adevice for hydrating particulate bone material, the device comprising atubular member having an interior surface configured to receive theparticulate bone material and a hydration fluid, the tubular memberhaving a proximal end opening configured to receive a syringe, and adistal end opening configured to receive a cap, the cap having aplurality of pores configured to allow the hydration fluid to flow intothe interior surface of the tubular member and hydrate the particulatebone material, the plurality of pores being smaller in size than theparticulate bone material, wherein the plurality of pores have a poresize from about 10 to about 100 microns.
 16. The device of claim 15,wherein the proximal end opening engages with a cap comprising a luerfitting that engages with the syringe.
 17. The device of claim 15,wherein (i) the particulate bone material is in a powder or a wet form;(ii) the particulate bone material has a particle size of 250 microns orless; or (iii) the particulate bone material is demineralized bone(DBM).
 18. A method of dispensing particulate bone material at asurgical site, the method comprising loading a device for hydrating theparticulate bone material, the device comprising a tubular member havingan interior surface and an exterior surface, the interior surfaceconfigured to receive the particulate bone material and a hydrationfluid, the exterior surface having a plurality of pores configured toallow the hydration fluid to flow into the interior surface of thetubular member and hydrate the particulate bone material, the pluralityof pores being smaller in size than the particulate bone material;immersing the device in a fluid filled bath; and slidably engaging thetubular member with a cannula and a plunger to dispense the particulatebone material to the surgical site.
 19. The method of claim 18, whereinthe proximal end opening of the tubular member comprises a collarconfigured to engage the cannula, or a proximal end of the cannulacomprises a collar configured to engage the tubular member.
 20. Themethod of claim 18, wherein the tubular member comprises a removabledistal end configured to form a distal end opening to dispense theparticulate bone material.